Diabetes insipidus and syndrome of inappropriate antidiuresis (SIADH) after pituitary surgery: incidence and risk factors.

Electrolyte disorders are relatively frequent and potentially serious complications after pituitary surgery. Both DI (diabetes insipidus) and SIADH (syndrome of inappropriate antidiuresis) can complicate and prolong hospital and intensive care unit stay, and the latter may even be preventable. We aim to assess the incidence of both electrolyte disorders and their risk factors. From a prospective registry of patients who underwent endoscopic transnasal transsphenoidal surgery (TSS) for pituitary adenoma, patients with postoperative DI and SIADH were identified. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of either DI or SIADH. A total of 174 patients were included, of which 73 (42%) were female. Mean age was 54 years (range 20-88). During postoperative hospital stay, 13 (7.5%) patients presenting with DI and 11 (6.3%) with SIADH were identified. Patients who developed DI after surgery had significantly longer hospital stays (p = 0.022), as did those who developed SIADH (p = 0.002). Four (2.3%) patients were discharged with a diagnosis of persistent DI, and 2 (1.1%) with the diagnosis of SIADH. At the last follow-up, 5 (2.9%) patients presented with persistent DI, while none of the patients suffered from SIADH. Younger age (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.01, p = 0.166) and pituitary apoplexy (OR 2.69, 95% CI 0.53-10.65, p = 0.184) were weakly associated with the occurrence of DI. We identified younger age (OR 0.96, 95% CI 0.92-0.99, p = 0.045) and lower preoperative serum sodium (OR 0.83, 95% CI 0.71-0.95, p = 0.008) as independent risk factors for SIADH. Although we found a weak association among age, pituitary apoplexy, and the occurrence of DI, no independent predictor was identified for DI. For postoperative SIADH however, lower age and preoperative serum sodium were identified as significant predictors. None of these findings were sufficiently supported by preexisting literature. Both electrolyte disorders are exquisitely hard to predict preoperatively, and further research into their early detection and prevention is warranted.

Intracranial germinoma causing cerebral haemiatrophy and hypopituitarism.

A young woman presented with primary amenorrhoea, progressive haemiparesis, visual disturbance, dementia and focal motor seizures. Investigations showed hypopituitarism, unilateral cerebral atrophy and inflamed cerebrospinal fluid. A trans-sphenoidal biopsy gave a unifying diagnosis of a pituitary germinoma.

Identification of thymosins ß4 and ß 10 in paediatric craniopharyngioma cystic fluid.

BACKGROUND: Adamantinomatous craniopharyngioma is the third most recurrent paediatric brain tumour. Although histologically benign, it behaves aggressively as a malignant tumour due to invasion of the hypothalamus and visual pathways. Surgery is still the first and almost the only mode of treatment, although serious damage can occur as a consequence of tumour localization. The proteomic characterization of the intracystic tumoural fluid could contribute to the comprehension of the tumorigenesis processes and to the development of therapeutic targets to reduce cyst volume, allowing less invasive surgery and/or delay of the radical resection of the tumour mass and the collateral serious effects. METHODS: Intracystic fluid was analysed by a LC-ESI-IT-MS top-down platform after acidification, deproteinization and chloroform liquid/liquid extraction. FINDINGS: Thymosin ß4 and ß10 peptides were for the first time identified in the intracystic fluid of adamantinomatous craniopharyngioma by low- and high-resolution MS analysis coupled with LC. The two peptides showed the same distribution trend in the analysed samples. Thymosin ß4 and ß10 were present in 77 % of the analysed samples. These peptides were not found in the cerebrospinal fluid available for two patients. INTERPRETATION: The presence of ß-thymosins in the intracystic fluid of the tumour confirmed the secretion of these proteins in the extracellular environment. Due to their G-actin-sequestering activity and antiapoptotic and anti-inflammatory properties, these peptides could be strictly involved in both tumour progression and cyst development and growth.

Case Report: Identification of Potential Prognosis-Related TP53 Mutation and BCL6-LPP Fusion in Primary Pituitary Lymphoma by Next Generation Sequencing: Two Cases.

Background: Primary pituitary lymphoma (PPL) is an extremely rare disease with poor prognosis. Although PPL has been shown to be different from classical primary central nervous system lymphoma because of the embryological origin of structures, individual and precise treatment of PPL remains unknown. Methods: A 61-year-old man and a 65-year-old woman both diagnosed with primary pituitary diffuse large B cell lymphoma underwent genetic analysis of cerebrospinal fluid and tumor tissue by next generation sequencing. Results: In the first case, partial remission was achieved following R²-MTX chemotherapy. In the other case with TP53 mutation and BCL6-LPP fusion, disease progressed although different chemotherapy regimens were given. Conclusion: The gene mutation of TP53 and BCL6 may be identified as a marker responsible for prognostic difference in patients with PPL. Genetic analysis may provide a novel approach for precise management and prognosis prediction.

Pituitary adenoma apoplexy with initial presentation mimicking bacterial meningoencephalitis: a case report.

Pituitary apoplexy is a rare but life-threatening disorder. Clinical presentation of this condition includes severe headache, impaired consciousness, fever, visual disturbance, and variable ocular paresis. Signs of meningeal irritation are very rare. However, if present and associated with headache, fever, and pleocytosis, meningeal irritation may lead to misinterpretation as infectious meningoencephalitis. To the best of our knowledge, pituitary apoplexy with an initial presentation mimicking infectious meningoencephalitis had rarely been reported in the literature. Here, we report a 57-year-old man who had acute severe headache, high fever, neck stiffness, disturbance in consciousness, and left ocular paresis. Laboratory data showed leukocytosis, an elevated C-reactive protein level, and neutrophilic pleocytosis in the cerebrospinal fluid. Because bacterial meningoencephalitis was suspected, empiric antibiotic therapy was administered but in vain. Further examinations indicated a diagnosis of pituitary adenoma with apoplexy. After the immediate administration of intravenous corticosteroid supplement and surgical decompression, the patient recovered.

Cerebrospinal fluid rhinorrhea following trans-sphenoidal pituitary macroadenoma surgery: experience from 592 patients.

OBJECTIVES: To determine the incidence, risk factors, diagnostic procedures, and management of cerebrospinal fluid (CSF) leaks following trans-sphenoidal pituitary macroadenoma surgery. METHODS: Retrospective analysis of 592 patients. RESULTS: Intra- and post-operative CSF leaks occurred in 14.2 and 4.4% of patients, respectively. Surgical revision, tumor consistency, and tumor margins were independently associated with intra-operative leaks, while the tumor size, consistency, and margins were risk factors of post-operative leaks. The intra-operative leak rate of ACTH adenomas was greater than all other types combined; the incidence of post-operative CSF leaks was highest for FSH adenomas. There were no significant differences among various techniques and we achieved an initial repair success rates of 83.3 and 92.9% for intra- and post-operative CSF leaks, respectively. Of the 26 patients with post-operative CSF leaks, five were complicated by meningitis and four by post-infectious hydrocephalus which required ventriculoperitoneal shunts. CONCLUSIONS: CSF leaks have a propensity to occur in cases with fibrous tumors or tumors with indistinct margin and may have some relationship with the tumor type. Endoscopic and microscopic repairs were shown to be effective techniques in managing these types of leaks. Post-infectious hydrocephalus may influence the outcome of the repair and ventriculoperitoneal shunts were necessary in some cases.

The relationship of polyamines in cerebrospinal fluid to the presence of central nervous system tumors.

Cerebrospinal fluid (CSF) polyamine concentrations were assayed in patients with and without central nervous system tumors, using a high-pressure liquid chromatographic technique. Definite elevations were found in the CFS polyamine concentrations of patients with untreated malignant central nervous system tumors when compared with those concentrations observed in the CSF of patients without neoplasia. Patients undergoing successful tumor therapy for malignant central nervous system tumors showed CSF polyamine concentrations that closely approximated the concentrations found in the CSF of patients without tumor.

Prolactin in human cerebrospinal fluid.

PRL was measured radioimmunologically in plasma and cerebrospinal fluid (CSF) samples obtained simultaneously in 31 patients with various neurological or infectious, but non-endocrine diseases (group A), 12 patients (7 pregnant women and 5 newborns) with physiological hyperprolactinemia (group B),10 psychiatric patients with pharmacologically induced hyperprolactinemia (group C) 12 normoprolactinemic patients with pituitary adenoma and suprasellar extension (SSE) (group D), And 14 hyperprolactinemic patients with pituitary adenoma with and without SSE (group E). Plasma PRL and CSF PRL concentrations (ng/ml, mean and range in brackets) of the various groups were: group A, 6.2 (1.3-14.5) and 1.3 (0.6-4.7); group B, 85.2 (31-200) and 13.2 (3-28); group C, 54.3 (3.5-160) and 6.5 (0.7-18); group D, 17.2 (5.4-30) and 9.7 (2.7-34); and group E, 2,529 (115-10,000) and 1,449 (6-13,000). The plasma to CSF concentration ratios (mean and range in brackets) were: group A, 5.2 (1.4-13.0); group B, 7.0 (2.9-10.3); group C, 7.3( 3.9-11.3); group D, 2.6 (0.9-7.1); and group E, 10.9 (0.2-34.9). The ratio was greater than 3 in 87% of the non-tumor patients; in 42% of the tumor patients the ratio was less than 3. The correlation between plasma and CSF PRL levels of all 53 subjects without a pituitary tumor (groups A, B, and C) was positive (r=0.9097; P=0.00001); in the 26 tumor patients (groups D and E) the correlation was also positive (r=0.7141; P=0.00002). These results indicate that 1) PRL is a normal constituent of CSF, 2) the CSF PRL level is a function of the plasma level, 3) detectable, or even high, CSF PRL levels per se are not indicative in the presence of a pituitary tumor, with or without SSE, and 4) abnormally low ratios may be found in patients with a pituitary tumor with SSE.

Polyamine levels in CSF from patients with pituitary tumors or nonneoplastic pituitary disease.

Cerebrospinal fluid polyamine determinations were performed in 21 patients harboring pituitary tumors and six patients with nonneoplastic pituitary disease. Although CSF putrescine levels were significantly elevated in some patients harboring tumors, other patients showed no elevation. Polyamine levels did not correlate with tumor size, as assessed by the presence or absence of suprasellar extension. Data on patients harboring nonneoplastic pituitary disease were variable. Compared with other findings from this laboratory on the use of polyamine levels for the diagnosis and management of other brain tumors, these findings suggest that CSF polyamine levels will not have a significant diagnostic role in the treatment of patients suspected to have pituitary disease.

Suprasellar extension of tumor associated with increased cerebrospinal fluid activity of growth hormone.

The diagnosis of hormonally active acromegaly has been aided by the radioimmunoassay for human growth hormone (hGH). We report a case in which baseline plasma hGH levels were elevated minimally and partial suppression during the glucose tolerance test occurred. Subsequent hGH assay of the cerebrospinal fluid, however, confirmed active acromegaly and correctly predicted suprasellar extension of the tumor.

Retention of dopamine 2 receptor mRNA and absence of the protein in craniospinal and extracranial metastasis of a malignant prolactinoma: a case report.

OBJECTIVES: The case presented here describes the clinical evolution of a malignant prolactinoma with occurrence of intra- and extra-cranial metastases. In this case, the presence of dopamine 2 receptor (D2R) was studied at the mRNA and protein level, in order to understand the pathological background of the resistance to treatment with different dopamine agonists. DESIGN: Together with an extensive description of the clinical history of this case, a combination of in vitro and in vivo techniques was performed to provide the basis of the dopamine resistance developed in the course of the disease. METHOD: A comparison of the D2R was performed in specimens obtained at presentation of the disease compared with autoptic specimens derived from local invasion and metastasis using in situ hybridization and immunohistochemical techniques. RESULTS: Intact D2R mRNA was found in the primitive tumor and metastatic tissues, whereas protein for the same receptor was present only in the tissues derived from neurosurgical operations and not in the metastases obtained post-mortem. CONCLUSION: This is the first report of the absence of D2R protein despite the retention of the transcript in an advanced stage of a malignant prolactinoma. The findings of this single case suggest the hypothesis that postranscriptional mechanisms may contribute to the development of dopamine resistance in prolactinomas.

Radioimmunoassay of human growth hormone: technique and application to plasma, cerebrospinal fluid, and pituitary extracts.

A radioimmunoassay for human growth hormone using activated charcoal is described and its precision, accuracy, and sensitivity are defined. Results are presented for growth hormone measurements in plasma obtained during hypoglycaemia induced with insulin in patients of short stature and during glucose tolerance tests in patients with acromegaly. The method was used to measure growth hormone concentrations in cerebrospinal fluid and in extracts of pituitary tumours. No growth hormone was detected in the cerebrospinal fluid of patients without acromegaly. In patients with acromegaly, the concentration of growth hormone in cerebrospinal fluid was measurable and was considerably elevated in one patient with extrasellar extension of a pituitary tumour. Extracts of chromophobe pituitary tumours contained very small concentrations of growth hormone. In extracts of pituitary tumours removed from acromegalic patients, concentrations fell either below or within the normal range.

The cerebrospinal fluid from patients with prolactinoma promotes neurite growth of sensory neurones.

The cerebrospinal fluid (CSF) of patients with hypophysis adenomas was used to investigate its effect on organotypic cultures of dorsal root ganglia (DRG) of 10-11 day old chick embryo. Only the CSF from patients with prolactinoma showed a neurite-stimulating effect compared with other hypophysis adenomas.

Anterior pituitary hormone levels in the cerebrospinal fluid of patients with pituitary and parasellar tumors.

Cerebrospinal fluid (CSF) concentrations of growth hormone, prolactin (PRL), adrenocorticotropin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and the glycoprotein hormone alpha subunit were determined in 30 patients with pituitary and parasellar tumors. Although many of the patients had elevated hormone levels, no differentiation between patients with intrasellar tumors and those with pituitary tumors with suprasellar extension or primary suprasellar tumors could be made based upon the absolute CSF hormone concentration. A highly significant correlation between serum and CSF PRL concentrations was found (r = 0.87; P less than 0.001), suggesting that CSF PRL is derived from the serum. No correlation was found between the serum and CSF concentrations of the other anterior pituitary hormones.

Suprasellar arachnoid cysts: 2. Evaluation of CSF dynamics.

Suprasellar arachnoid cysts are an infrequent but surgically remediable cause of hydrocephalus and neurologic deficits. The optimal method of treatment varies according to whether the cyst communicates with the subarachnoid space; the presence or absence of associated hydrocephalus; and the exact site(s) and severity of intraventricular and extraventricular cerebrospinal fluid (CSF) obstruction. Eight patients with suprasellar arachnoid cysts are described to emphasize the importance of pretherapeutic investigation of CSF dynamics. The variability of the ventriculocisternal-cyst CSF dynamics and the value of metrizamide computed tomographic cisternography and ventriculography in investigation of the CSF pathways are stressed. A diagnostic approach to the evaluation of the CSF dynamics is outlined, based on whether hydrocephalic or compressive symptoms predominate.

Radioimmunoassay of insulin-like growth factors I and II in the cerebrospinal fluid of patients with pituitary and other central nervous system tumors.

Tumor cells are characterized by abnormalities in growth and metabolism, including the autocrine secretion of certain growth factors. On the basis of our previous demonstration of the production of insulin-like growth factors (IGFs) and their binding proteins by central nervous system (CNS) tumors, we asked whether the levels of IGFs in the CSF may be altered in patients with pituitary and other CNS tumors and may reflect autocrine secretion. We used specific radioimmuoassays for IGF-I and -II and measured these growth factors in the cerebrospinal fluid (CSF) from 26 patients with tumors located adjacent to the ventricular system. The tumors included were eight pituitary tumors (five nonsecreting, three growth hormone secreting), five gliomas, two meningiomas, five medulloblastomas, three metastases, and three other tumors. CSF from patients without tumors served as controls. For radioimmunoassay, CSF was treated with acetic acid overnight and IGF-binding proteins were separated from IGFs by C-2 solid phase cartridge extraction. The pituitary tumors were characterized by significantly elevated levels of IGFs in the CSF. In nonseceting pituitary tumors, the levels of IGF-I in the CSF were similar to normal levels, whereas IGF-II levels were significantly elevated. In acromegalic patients, levels of both IGF-I and -II in the CSF were significantly elevated compared with normal levels and compared with levels in patients with nonsecreting tumors. In contrast, the levels of IGFs in the CSF from most of the primary and metastatic CNS CNS tumors did not significantly differ from normal values. In summary, although IGFs may contribute to the regulation of cell growth in primary CNS tumors, CSF levels are not elevated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal fluid rhinorrhea as a presentation of pituitary adenoma.

We report a patient with a pituitary adenoma who presented with only cerebrospinal fluid rhinorrhea. A radiologically unrecognized defect in the floor of the sella was observed at operation.

CSF prolactin determination in patients following operation for pituitary tumor.

Serial cerebrospinal fluid (CSF) and plasma prolactin concentrations were determined from patients during prolactin stimulatory testing with thyrotropin-releasing hormone or during pneumoencephalographic stress. Six patients had been operated on for suprasellar extension of pituitary tumor and one had been irradiated for suprasellar extension of a pituitary tumor. Prior to testing, four patients had had no clinical evidence of tumor recurrence and 3 patients had had tumor recurrence. One of the recurrent tumors had again extended into a suprasellar location. Basal CSF prolactin was undetectable in all patients who had had no recurrence. In 3 of the 4 patients without recurrence, however, prolactin became detectable in CSF during stimulatory testing. CSF prolactin values also increased during stimulatory testing in the patient with suprasellar recurrence of the tumor. A basal CSF-to-plasma prolactin ratio was 0.1 or less in all patients without recurrence. In the 2 patients with recurrence but without suprasellar extension, the CSF-to-plasma prolactin ratio was 0.18 or less. The patient with suprasellar recurrence had a strikingly elevated CSF-to-plasma prolactin ratio of 1.1. Thus, an increase of CSF prolactin during stimulatory testing does not necessarily indicate suprasellar recurrence of a pituitary tumor. However, an elevated CSF-to-plasma prolactin ratio appears to remain a valid indicator of suprasellar extension despite prior pituitary surgery.

[Determination of 6 pituitary hormones in the cerebrospinal fluid. Control subjects, prolactin adenomas, empty sella syndrome and hypothalamic disorders (author's transl)]. / Dosage de 6 stimulines hypophysaires dans le liquide céphalo-rachidien. Sujets normaux, adénomes à prolactine, selles vides, syndromes hypothalamiques.

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I-12 normal subjects (6 males and 6 females); II-12 prolactin adenomas (3 males and 9 females); III-5 empty sella syndromes, 3 hypothalamic disorders, 1 chromophobe adenoma, 1 pituitary dwarfism. It is concluded that: 1) pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level. 2) there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level. 3) in prolactin adenomas, only prolactin is elevated in the CSF. 4) there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.

[Determination of pituitary hormones in cerebrospinal fluid in normal subjects and in hypothalamo-pituitary diseases. Secreting or non-secreting pituitary adenoma, empty sella syndrome, hypothalamic syndromes]. / Le dosage des stimulines hypophysaires dans le liquide céphalo-rachidien chez le sujet normal et en pathologie hypothalamo-hypophysaire. Adénome hypophysaire sécrétant ou non sécrétant, selle turcique vide, syndromes hypothalamiques.

Cerebrospinal fluid (CSF) and serum concentrations of TSH, ACTH, FSH, LH, GH and PRL were measured simultaneously in 34 subjects divided into 3 groups: I--12 normal subjects (6 males and 6 females); II--12 prolactin adenomas (3 males and 9 females); III--5 empty sella syndromes; 3 hypothalamic disorders; 1 chromophobe adenoma; 1 pituitary dwarfism. It is concluded that:--pituitary hormones are the normal constituents of CSF but the level can be undetectable and in any case lower than the serum level; --there is a positive correlation between serum and CSF concentration of PRL when serum PRL is higher than 20 ng/ml, indicating that the CSF level is influenced by serum level; --in prolactin adenomas only prolactin is elevated in the CSF; --there is no correlation between the high level of CSF-PRL and a suprasellar extension of the adenoma.